Efficacy and Safety of Eliapixant in Refractory Chronic Cough: The Randomized, Placebo-Controlled Phase 2b PAGANINI Study

• DOI: 10.1007/s00408-023-00621-x
• Publication Date: 2023-06-01T15:02:02Z
• Authors: Peter V. Dicpinig...; Alyn H. Morice; Jaclyn A. Smith; Mandel R. Sher; Michael Vaezi; Laurent Guillemin...; Akio Niimi; Kerstin Gude; Ulrike Krahn; Riitta Saarinen; Philippe Vieira P...; Melanie Wosnitza; Lorcan McGarvey
• Keywords: Dysgeusia; Discontinuation; Tolerability; Clinical endpoint; Refractory (planetary science)

The PAGANINI study evaluated the efficacy and safety of the selective P2X3 antagonist eliapixant in patients with refractory chronic cough (RCC).PAGANINI was a randomized, double-blind, parallel-group, placebo-controlled, multicenter, dose-finding, phase 2b study. Adults with RCC lasting ≥ 12 months and cough severity ≥ 40 mm on a visual analog scale at screening were enrolled. Participants were randomized 1:1:1:1 to twice-daily 25 mg, 75 mg, or 150 mg oral eliapixant or placebo for 12 weeks. The primary endpoint was change from baseline in 24-h cough count after 12 weeks of intervention.Overall, 310 participants were randomized to twice-daily eliapixant 25 mg (n = 75), 75 mg (n = 78), 150 mg (n = 80), or placebo (n = 77). A statistically significant dose-response signal with eliapixant was detected for the primary endpoint (all dose-response models, adjusted p < 0.1; one-sided). Adverse events (AEs) were reported in 39 (51%) participants with placebo and 43-51 (57-65%) participants receiving eliapixant. The most common AE was dysgeusia, occurring in 1% (n = 1) of the placebo group and 1-16% (n = 1-13) of the eliapixant groups in a dose-related manner. One case of a moderate drug-induced liver injury occurred in a participant receiving 150 mg twice-daily eliapixant.Eliapixant demonstrated efficacy and a favorable taste tolerability profile in RCC. However, a drug-induced liver injury contributed to intensified liver monitoring in clinical trials with eliapixant and discontinuation of the entire development program in all indications by Bayer AG.ClinicalTrials.gov identifier NCT04562155; registered September 18, 2020.